In March 2009, cases of influenza-like illness in Mexico caused by a novel H1N1 virus containing genes from swine, avian, and human influenza strains were reported. Within several weeks, 2009 H1N1 disseminated rapidly and was the predominant influenza strain globally. On June 11, 2009, the World Health Organization declared that criteria for an influenza pandemic had been met. Concern that this pandemic would rival the 1918 pandemic was high. Fortunately, that was not the case. Influenza-related disease activity peaked in late October to November 2009. By August 2010, the H1N1 influenza virus had moved into the postpandemic period. During the 2010-2011 season, influenza A H3N2 has been the predominant serotype, but the 2009 H1N1 continues to co-circulate with H3N2 and B strains. In contrast to previous seasonal influenza strains, the novel 2009 H1N1 strain preferentially affected young adults, with a clustering of severe and fatal cases in adults between the ages of 30 and 50 years. Additionally, H1N1 displayed a heightened potential for severe lung injury as well as gastrointestinal symptoms. Risk factors for severe disease included obesity, morbid obesity, pregnancy, immunosuppression, asthma (in children), chronic obstructive pulmonary disease, neurological disorders, other comorbidities, HIV-infection, poverty, and lack of access to care. However, >25% of deaths were in previously healthy individuals. Molecular tools for identifying 2009 H1N1 were rapidly developed, but the volume of samples quickly overwhelmed available laboratory services. Further, in the early phases of the pandemic, the volume of patients presenting to emergency rooms, acute care clinics, and physician's offices overwhelmed health care resources. Fortunately, most cases were mild; in the United States, only one in 400 required intensive care unit care, and one in 2000 died. Because most infected individuals have mild, self-limited disease, the risk/benefit assessment for early access to antiviral agents must balance the potential benefit for reducing transmission, disease severity, and burden on health care providers against the potential for dissemination of viral resistance and drug-related adverse events. Monovalent vaccines against 2009 H1N1 were developed and ready for distribution by September 2009, but initial supplies were inadequate to impact the bulk of cases that occurred in the Northern Hemisphere between April and September 2009. Continued efforts to develop universal vaccines and improve access to effective vaccines are critical.